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Table 1 Effect of curcumin and curcumin analogues in colorectal cancer stem cells: in vitro and in vivo (mice models) studies

From: Targeting colorectal cancer stem cells using curcumin and curcumin analogues: insights into the mechanism of the therapeutic efficacy

Study

Authors

Title

Journal and year

In vitro study

In vivo study (Mice)

Experimental design

Results

1

Lin et al.

Targeting colon cancer stem cells using a new curcumin analogue, GO-Y030 [78]

British Journal of Cancer, 2011

Yes

Yes

ALDH+/CD133+ colon CSC were isolated from DLD1, HCT-116, and SW480 and HT29 colon CSC by flow cytometry. These cells were treated with GO-Y030 and cell death was observed by flow cytometry and tumourspheres were counted in the differentiating medium. These cells of SW480 and HCT-116 were injected subcutaneously into mice models and observed

GO-Y030 inhibited STAT 3 phosphorylation, cell viability, and tumoursphere growth of CSC in vitro. It suppressed tumour growth of CSCs from both SW480 and HCT-116 colorectal cancer cell lines in vivo in mice model

2

Wang et al.

Novel micelle formulation of curcumin for enhancing antitumour activity and inhibiting colorectal cancer stem cells [79]

International Journal of Nanomedicine, 2012

Yes

Yes

Cells obtained from cell cultures or xenograft tumours labeled with CD44-APC and CD24-FITC were treated with curcumin encapsulated in stearic acid-g-chitosan oligosaccharide (CSO-SA) and free curcumin and compared. Intravenously CSO-SA was injected into the mice

In vitro, CSO-SA showed anti-proliferative effects, 6× greater than free curcumin. In vivo, it suppressed tumour growth

3

Kanwar et al.

Difluorinated-curcumin (CDF): a novel curcumin analog is a potent inhibitor of colon stem-like cells [42]

National Institute of Health, 2011

Yes

No

Chemo-resistant cells of HCT-116 and HT-29 treated with 5FU + Ox alone or in combination with curcumin or CDF were compared. CDF showed more inhibition of transporter protein, growth factor receptor attenuation

CDF together with 5-FU + Ox was more potent than curcumin in reducing CD44, CD166 in chemo-resistant colon cancer cells by inhibition of growth, apoptosis induction and disintegration of colonospheres

4

Nautiyal et al.

Combination of Dasatinib and curcumin eliminates chemo-resistant colon cancer cells [43]

Journal of Molecular Signalling, 2011

Yes

No

Chemo-resistant cells of HCT-116 and HT-29 were treated with Dasatinib and curcumin. Dose comparison was done for Dasatinib with and without curcumin

The combination therapy of Dasatinib and curcumin showed better inhibition of cell growth, invasion, and colonosphere formation and reduced CSC population by reduced expression of CSC specific markers

5

Yinjie Yu et al.

Elimination of colon cancer stem-like cells by the combination of curcumin and FOLFOX [44]

Translational oncology, 2009

Yes

No

FOLFOX-surviving colon cancer cells of HCT-116 line were used with media containing FOLFOX or curcumin or combination to analyze the protein levels of CD44 and CD166

Treatment of FOLFOX surviving colon cancer cells with combination of curcumin and FOLFOX resulted in marked reduction of CSCs, reduction in colonospheres, increased expression of EGFR

6

Buhrmann et al.

Curcumin suppresses crosstalk between colon cancer stem cells and stromal fibroblasts in the tumour microenvironment: potential role of EMT [80]

PloS One, 2014

Yes

No

HCT-116 was co-cultured with MRC-5 cells in a high density microenvironment to mimic the CSC/fibroblast interactions in vivo and treated with 5-FU and/or curcumin in concentration-dependent manner

Co-cultured HCT-116 and MRC-5 cells showed synergistic interaction, indicated by the expression of molecules/proteins involved in tumour progression. Curcumin interferes with the cross-talk by interfering with their regulations/expressions

7

Roy et al.

Difluorinated-curcumin (CDF) restores PTEN expression in colon cancer cells by down-regulating miR-21 [81]

PloS One, 2013

Yes

No

Fu-OX resistant cells generated in HCT-116, HT-29 and SW620 and the expression of miR-21 and PTEN protein measured after CDF treatment

Xenograft tissue from SCID mouse transfected with miR-21 was also analysed for the expression of miR-21 and PTEN for comparison purposes

CDF restores PTEN expression by down-regulating miR-21 expression in Fu-Ox resistant cells from the colonosphere population, which showed overexpression of miR-21 and decreased levels of PTEN prior to CDF treatment